Biophysical measurement of brain tumor cohesion

Abstract

An advantage of using 3D multicellular spheres to study tumor biology is that they better approximate the interactions encountered by cells in vivo. Our previous studies have shown that the process of spheroid formation is governed by the same thermodynamic principles driving the formation of liquid droplets. This liquid-like behavior enables us to measure a key property influencing tumor behavior, namely, intercellular cohesion. We have developed a method, tissue surface tensiometry (TST), to measure the cohesivity, expressible as surface tension (), of tissue aggregates under physiologic conditions. This study utilizes TST to measure the cohesivity of 3 widely used malignant astrocytoma cell lines of different in vitro invasive potentials. We compare invasiveness with aggregate cohesivity and with the expression of N-cadherin, a key mediator of cell-cell cohesion in neural tissues. We show that the cell lines exhibit liquid-like behavior since they form spheroids whose surface tension is both force-and volumeindependent; that aggregates from each cell line have a distinct surface tension that correlates with their in vitro invasive capacity; that dexamethasone (Dex), a widely used therapeutic agent for the treatment of tumor-related cerebral edema, increases aggregate cohesivity and decreases invasiveness; that dexamethasone treatment decreases invasion in a dose-dependent manner but only when cells are in direct contact with one another; and that dexmediated decreased invasiveness correlates with increased aggregate cohesivity as measured by TST but not with N-cadherin expression or function. Our results demonstrate that for these cell lines, cohesivity is an excellent predictor of in vitro invasiveness. © 2004 Wiley-Liss, Inc. Key words: tissue surface tensiometry; malignant astrocytoma; cohesivity; invasion; dexamethasone Glioblastoma multiforme (GBM) represent approximately 60% of all gliomas and 30% of all intracranial tumors. 1 The hallmark of these aggressive tumors is their ability to invade the brain rapidly. Typically, at the time of diagnosis, tumor cells have already spread at least 2 cm beyond the main tumor mass. This rapid local invasion, along with their intrinsic resistance to radiation and chemotherapy, is one of the key factors in primary brain tumor resistance to current forms of therapy. Unfortunately, the current system of histopathologic staging provides a poor approximation of the behavior of an individual tumor. Some histologically lowgrade tumors rapidly invade the brain, while some tumors graded histologically as aggressive do not behave as aggressively as their histology would predict. Newer molecular classifications of brain tumors as yet have failed to provide a more accurate prediction of tumor behavior.Molecular mechanisms underlying malignant brain tumor invasion have been intensively studied over the last 20 years. Many factors have been identified as either facilitators or inhibitors of brain tumor invasion, including cytokines, 2 lymphokines, 3 adhesion molecules, 4 growt...

An elasto-visco-plastic model of cell aggregates

“…Using this approach, Iordan et al [20] were able to determine typical intrinsic properties for concentrated suspensions of Chinese Hamster Ovary cells (CHO). Other works deal with different types of cell suspensions [10,12,11,13,42], and similar behaviors are observed. Their interpretation of the experimental data is usually given in terms of a macroscopic mechanism, i.e.…”

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“…Steady shear is considered in Section 4.1 where the results are compared with relevant data [20], stress relaxation and oscillatory shear tests are discussed in Sections 4.2 and 4.3, elastic recovery after shear is illustrated in Section 4.4. In the last section, compression experiments taken from the literature [10,12,13,42] are re-considered in the framework of this new model.…”

Multiphase Models of Tumour Growth

“…In fact, from the experimental point of view it is very difficult to perform mechanical tests on living matter, and in particular on ensembles of cells. In this respect Winters et al [WSF05] performed a wonderful and very promising experiment consisting in a uniaxial compression test. More precisely, multicellular spheroids with radii in the range 0.15-0.7 mm were positioned between two plates immersed in a physiological liquid.…”

Tissue surface tensions guide in vitro self‐assembly of rodent pancreatic islet cells

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